Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells immunotherapy combined with chemotherapy for treatment of colorectal cancer in China: a meta-analysis of 29 trials involving 2,610 patients

Abstract

PurposeTo systematically evaluate the efficacy and safety of Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells (CIK/DC-CIK) immunotherapy in treating advanced colorectal cancer (CRC) patients.Results29 trials including 2,610 CRC patients were evolved. Compared with chemotherapy alone, the combination of chemotherapy with CIK/DC-CIK immunotherapy significantly prolonged the overall survival rate (OS) and disease-free survival rate (DFS) (1–5 year OS, P < 0.01; 1-, 2-, 3- and 5-year DFS, P < 0.01). The combined therapy also improved patients’ overall response, disease control rate and life quality (P < 0.05). After immunotherapy, lymphocyte subsets percentages of CD3+, CD3−CD56+, CD3+CD56+ and CD16+CD56+ (P < 0.01) and cytokines levels of IL-2 and IFN-γ (P < 0.05) were increased, while CD4+, CD8+ and CD4+CD25+ and IL-6 and TNF-α did not show significant change (P > 0.05).Materials and MethodsClinical trials reporting response or safety of CIK/DC-CIK immunotherapy treating advanced CRC patients and published before September 2016 were searched in Cochrane Library, EMBASE, PubMed, Wanfang and CNKI database. Research quality and heterogeneity were evaluated before analysis. Pooled analyses were performed using random or fixed-effect models.ConclusionsThe combination of CIK/DC-CIK immunotherapy and chemotherapy prolong CRC patients’ survival time, enhanced patients’ immune function and alleviates the adverse effects caused by chemotherapy.

Clinical applications of dendritic cells&ndash;cytokine-induced killer cells mediated immunotherapy for pancreatic cancer: an up-to-date meta-analysis

“…Previous study has reported the immunosuppressed status in cancer patient, and several researchers found that adjuvant immunotherapy of DC–CIK was able to enhance the efficacy of chemotherapy for various malignant tumors by reconstructing cancer patient’s immune function. 5 , 6 Our analysis showed that DC–CIK treatment can significantly improve the percentages of CD3 + , CD4 + , and CD3 + CD56 + T cells in PC patients. Moreover, CD4 + CD25 + CD127 low regulatory T cells negatively regulate the antitumor activity of DC–CIK immune cells 36 and our analysis showed result that CD4 + CD25 + CD127 low regulatory T-cell subset proportion decreased after DC–CIK immunotherapy.…”

“…Heterogeneity among studies was assessed to determine suitable analysis model. 5 , 22 Cochran’s Q test was performed to evaluate the homogeneity, and funnel plots were used to assess the publication bias of included studies. I 2 <50% or P >0.1 indicated that the studies were homogenous.…”

“…Adoptive cellular immunotherapy has demonstrated efficacy for the treatment of various malignant tumors, especially dendritic cells–cytokine-induced killer (DC–CIK) cells mediate immunotherapy. 5 , 6 Compared to immunotherapy using other types of cells, such as lymphokine-activated killer (LAK) cells, 7 , 8 natural killer (NK) cells, 9 , 10 and other immune cells, 11 , 12 DC–CIK-mediated immunotherapy exhibited a stronger antitumor ability and broader antitumor spectrum. 13 , 14 Cytokine-induced killer (CIK) cell is a heterogeneous subset of T lymphocytes, which primarily consist of CD3 + CD56 + cells and is easy to be collected from human peripheral and umbilical cord blood, and subsequently induced by IFN-γ, anti-CD3 monoclonal antibodies (OKT-3), and IL-2 in vitro.…”

“…DC have the capacity to enhance CIK’s cytotoxicity by coculture with CIK cells, which is indicated by increased proportion of CD3 + CD56 + cells and improved levels of cytokines such as IFN-γ and IL-2. 5 , 15 …”

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

“…Several studies have shown the following effects of NK cells in different cancers: NK cells have been shown to be effective in patients with advanced lung cancer; Herceptintreated NK cells have been found to have therapeutic potential in the treatment of patients with human epidermal growth factor receptor 2 (Her2 + ) and Herceptin-intolerant breast cancer; expanded and cryopreserved NK cells are promising candidates for cellular immunotherapy in patients with pancreatic carcinoma; NK cells inhibit metastesis of ovarian carcinoma cells in murine models; CIK cells may become a novel therapeutic modality for rhabdomyosarcoma after allogeneic HSCT; CAR-engineered CIK cells may become valuable in the treatment of HR soft tissue sarcoma in children; and expanded and CIK cells are safe and well tolerated and they enhance cytotoxicity against gastric carcinoma [162,[265][266][267][268][269][270][271]. A meta-analysis, that included 29 clinical trials involving 2610 patients, has been shown that the combination of CIK/DC-CIK immunotherapy and cytotoxic chemotherapy: enhances the immune function of patients, alleviates the adverse effects of chemotherapy, and improves the overall response, disease control, and quality of life [272].…”